Rational nanocarrier design towards clinical translation of cancer nanotherapy

The past decades have witnessed an exponential growth in research of cancer nanomedicine, which has evolved into an interdisciplinary field involving chemistry, physics, biology, and pharmacology, pathophysiology, immunology and clinical science in cancer research and treatment. The application of nanoparticles in drug delivery increases the solubility and decreases the toxicity of free drug molecules. The unique feature of cancer pathophysiology, e.g. leaky blood vessel, presents a unique opportunity for nanocarriers to deliver therapeutics selectively to tumor sites based on size selectivity. However, the clinical translation of nanomedicine is mostly limited to the classical liposomal formulations and PEGylation of therapeutics. Numbers of reasons hinder the clinical translation of the novel nanoparticles developed in the last decades for drug delivery. Comprehensive understanding of the properties of nanocarriers and their interactions with the physiological and pathological interfaces is critical to design effective nanoformulations. In addition, understanding the general principles and concerns in pharmaceutical industries and clinical practice for nanotherapeutic development is essential to develop a translatable nanoformulations via rational nanocarrier designs. In this account, we will review the relationship between the physiochemical properties of nanocarriers and biodistribution, and interactions with biological and immunological systems for effective drug delivery and cancer treatments. Further, we review the strategies for rational design of nanocarriers via structure-based approach and bio-mimicking systems to facilitate the clinical translation in enhancing cancer treatment via both chemotherapy and immunotherapy.